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Utility of homology models in the drug discovery process
TLDR
An overview of the latest developments in homology modeling techniques is provided and includes selected examples of successful applications of thehomology modeling technique to pharmaceutically relevant questions. Expand
Dissecting Physiological Roles of Estrogen Receptor α and β with Potent Selective Ligands from Structure-Based Design
TLDR
This work designed steroidal ligands that exploit the differences in size and flexibility of the two ligand binding cavities and synthesized and tested compounds predicted to bind preferentially to either ERα or ERβ, leading to highly ER isotype-selective and potent ligands. Expand
A New Mode of Mineralocorticoid Receptor Antagonism by a Potent and Selective Nonsteroidal Molecule*
TLDR
It is proposed that BR-4628 is a bulky antagonist that inactivates MR through a passive mechanism and represents the prototype of a new class of MR antagonists. Expand
Conception and pharmacodynamic profile of drospirenone
TLDR
DRSP prevented the mild increase of blood pressure seen under a conventional levonorgestrel-containing contraceptive and even tended to reduce pretreatment blood pressure, and powerful antiandrogenic effects were seen in gonad intact and testosterone substituted castrated male rats. Expand
Discovery of BAY 94‐8862: A Nonsteroidal Antagonist of the Mineralocorticoid Receptor for the Treatment of Cardiorenal Diseases
TLDR
An extended SAR exploration starting from cyano‐1,4‐dihydropyridines that were identified by high‐throughput screening led to the identification of a dihydronaphthyridine, BAY 94‐8862, which is a potent, selective, and orally available nonsteroidal MR antagonist currently under investigation in a clinical phase II trial. Expand
Dissecting physiological roles of estrogen receptor alpha and beta with potent selective ligands from structure-based design.
TLDR
In vivo experiments with rats were conducted using the ERalpha- and ERbeta-selective agonists in comparison to 17beta-estradiol, and it can be concluded that estrogen effects on the uterus, pituitary, bone, and liver are primarily mediated via ERalpha. Expand
Recent advances in FRET: distance determination in protein-DNA complexes.
TLDR
Advances in the preparation of dye-labeled nucleic acid molecules and in new techniques, such as the measurement of FRET in polyacrylamide gels or in vivo, will lead to an increasingly important role of F RET in structural and molecular biology. Expand
Binding Free Energy Calculations for Lead Optimization: Assessment of Their Accuracy in an Industrial Drug Design Context.
TLDR
This work analyzed the performance of the molecular mechanics continuum solvent, the linear interaction energy (LIE), and the thermodynamic integration (TI) approach for three sets of compounds from industrial lead optimization projects, finding no method was sufficiently predictive when applied out of the box without considering challenges. Expand
Improving the hit-to-lead process: data-driven assessment of drug-like and lead-like screening hits.
TLDR
This work describes how to break down large numbers of screening hits and provides a comprehensive overview of the strengths and weaknesses for each structural class. Expand
Impact of isotype-selective estrogen receptor agonists on ovarian function.
TLDR
In intact rats, E2 and the ERα agonist dose-dependently inhibited ovulation, in contrast to the ERβ agonist, implying that direct estrogen effects on ovarian follicular development are mediated by ERβ. Expand
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